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ERBB2 S310F mutation independently activates PI3K/AKT and MAPK pathways through homodimers to contribute gallbladder carcinoma growth

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Abstract

Genomic instability and mutability are a prominent character of tumor. The whole-exosome sequence reveals that ERBB2 mutations are the representative mutations of gallbladder carcinoma, which takes potential targets for gallbladder carcinoma therapy. However, the roles of ERBB2 mutations are unclear in gallbladder carcinoma. We identified S310F mutation is the hottest mutation of ERBB2 mutations from TCGA PanCancer Altas data with 10,967 samples and our previous study with 157 gallbladder carcinoma samples. S310F mutation located in ERBB2 extracellular domain, promoted ERBB2 homodimerization and consequent auto-phosphorylation to activate the downstream PI3K/AKT and MAPK pathways, which was independent on ERBB1, ERBB3, and ERBB4. ERBB2 S310F mutation up-regulated aerobic glycolysis and promoted gallbladder carcinoma growth. Our study reveals the roles of ERBB2 S310F mutation, which is beneficial to ERBB2 S310F mutant gallbladder carcinoma therapy.

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Funding

This work was supported by National Natural Science Foundation of China Grants (81802751, 82072682). All authors have contributed to this study.

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Authors and Affiliations

  1. Department of General Surgery, Central Hospital of Xuhui District, Shanghai, People’s Republic of China

    Kun Fan, Sheng Shen & Houbao Liu

  2. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

    Kun Fan, Jiwen Wang, Sheng Shen, Xiaojian Ni, Zijun Gong, Bohao Zheng, Wentao Sun, Tao Suo, Han liu, Xiaoling Ni & Houbao Liu

  3. Biliary Tract Disease Center of Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

    Kun Fan, Jiwen Wang, Sheng Shen, Xiaojian Ni, Zijun Gong, Bohao Zheng, Wentao Sun, Tao Suo, Han liu, Xiaoling Ni & Houbao Liu

  4. Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

    Kun Fan, Jiwen Wang, Sheng Shen, Xiaojian Ni, Zijun Gong, Bohao Zheng, Wentao Sun, Tao Suo, Han liu, Xiaoling Ni & Houbao Liu

  5. Biliary Tract Disease Institute, Fudan University, Shanghai, People’s Republic of China

    Kun Fan, Jiwen Wang, Sheng Shen, Xiaojian Ni, Zijun Gong, Bohao Zheng, Wentao Sun, Tao Suo, Han liu, Xiaoling Ni & Houbao Liu

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  1. Kun Fan
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Correspondence to Houbao Liu.

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Fan, K., Wang, J., Shen, S. et al. ERBB2 S310F mutation independently activates PI3K/AKT and MAPK pathways through homodimers to contribute gallbladder carcinoma growth. Med Oncol 39, 64 (2022). https://doi.org/10.1007/s12032-021-01568-w

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